The broad long-term of this project is to develop methods for evaluation of adherence to intravaginal microbicide therapy for the prevention of HIV transmission. Correct determination of adherence to preventative therapies in clinical trials is essential to accurate evaluation of efficacy. A better understanding of the true adherence to a preventative therapy will lead to the development of products with higher acceptability, and provide insight into the relationship between self-reported use of preventative therapy and actual use. Current methods of adherence evaluation for vaginal microbicide trials include self-reporting by study participants, physician or health care provider assessment, and inspection of study materials (gel applicators or used intravaginal rings) returned during clinic visits. All of these methods are prone to inaccuracy as indicated by the over-reporting of adherence observed in several clinical trials when adherence metrics were compared to trial outcomes. The proposed adherence-monitoring intravaginal ring (adherence IVR) will allow the direct measurement of adherence to IVR-delivered microbicide therapy by monitoring IVR temperature, conductivity, or both continuously on a half-hourly to hourly timescale to determine if the IVR is being worn or not during a clinical trial. The adherence IVR will contain a miniaturized module for sensing temperature (IVR at body temperature when in and below when out) and conductivity (IVR wetted and conductivity high when in, IVR dry and conductivity low when out) to determine adherence state. A microcontroller circuit embedded completely in the silicone ring structure will process the sensor data and store a digital adherence state (1 = IVR in, 0 = IVR out) to non-volatile memory at a fixed time interval. When the ring is removed, typically monthly, the adherence data may be downloaded from the IVR to a laptop computer or other device (smart phone or tablet) to provide a record of adherence that is free from reporting bias. The project has three principal objectives: (1) development of the microcontroller and sensor electronics and embedded software for sensor signal processing, conversion to digital adherence values, and logging to non-volatile memory for subsequent retrieval; (2) incorporation of this adherence monitoring functionality into a pod-IVR for intravaginal delivery of the microbicide tenofovir; and (3) evaluation of adherence monitoring performance, preliminary safety, and pharmacokinetics of tenofovir delivery in a sheep model. At the conclusion of this Phase I effort, a novel method for evaluating adherence to IVR microbicide therapy for prevention of HIV transmission will have been designed, fabricated, and evaluated in an animal model. The adherence-monitoring technology developed here may be extended to other pod-IVR delivery devices (i.e. microbicide combinations) and other IVR platforms.